The research program addresses the form and functions of membrane systems (sarcoplasmic reticulum (SR) and transverse-axial tubular system (TATS) of a variety of different mammalian hearts. Four major research foci are involved: (1) documentation of the mode(s) and time(s) of formation of membrane systems and their subdivisions during embryonic and postnatal development; (2) determination of the volume and surface area contributions of membrane systems in different regions of developing and adult hearts; (3) correlation of electrophysiological proparties of developing and adult hearts with the results of (1) and (2); (4) elucidation of structural details of membrane system elements, particularly the specialized complexes known as couplings. These aims will be carried out through the use of electron microscopy (TEM, HVEM, and SEM), in combination with specialized techniques (cytochemical regimens, stereology, stereoscopy, freeze-fracture, and X-ray analysis among them) and in correlation with electrophysiological recordings. A major purpose is to determine whether the configuration, amounts, and distribution of the membrane system elements is positively related to basic physiological characteristics of the hearts under examination, including heart rate, development of action potential characteristics, and reactivity to cardiac glycosides. Stereological studies will also examine changes in substructure of couplings under conditions of stimulation. Hearts of mouse, guinea pig, and rat will provide the bulk of material for the study of development, configuration, and contribution of membrane systems. The first two rodents are chosen because of the considerable differences between time-frame and ultimate degree of development of their membrane systems. Rat heart is intermediate in development between the first two, and--like them--has been a mainstay of research on the heart (even though it possesses physiological and pharmacological properties distinctly different from many other mammals). Least shrews will be examined because this animal is a primitive mammal with an extreme heart rate (up to 1200 beats/min). Primate hearts also will be utilized, in the expectation that the developmental, cytochemical, and morphometric approaches of this program of research will be applied to their cells and membrane system, because of their especial relevance to the understanding of functioning of human heart.